A two-step algorithm for Clostridioides difficile infection (CDI) testing may reduce unnecessary treatment and improve detection, while uncovering the secrets of the gut microbiome may hold the key for treating recurrent CDI (rCDI), according to the findings of recent studies.
Current guidelines recommend a multistep approach to increase specificity and sensitivity when testing for CDI, so researchers sought to evaluate results from switching to a two-step workflow from a one-step for C. difficile testing on CDI treatment in a large community health system. The findings were shared at ECCMID 2023: the European Congress of Clinical Microbiology & Infectious Diseases, held in Copenhagen, Denmark (abstract E0231).
“Clostridioides difficile is a significant burden for both the healthcare system, because of our increased expenditures, as well as for the patients—from an increased mortality, increased morbidity standpoint. And we do know that guidelines recommend a multistep approach for C. diff testing compared with utilizing a single step alone,” said study researcher Olivia Knack, PharmD, a PGY-1 clinical pharmacist at Amita Health Saints Mary and Elizabeth Medical Center, in Chicago.
The researchers retrospectively assessed the transition of multiple centers from a one-step (polymerase chain reaction [PCR]) to a two-step algorithm (PCR plus toxin A/B reflex) for the evaluation of CDI. The pre-implementation period was from Nov. 20, 2020 to May 6, 2021, and the post-implementation period spanned from July 2 to Dec. 26, 2021. Those who received stool softeners/laxatives within 48 hours of testing, selected concomitant medications, and CDI diagnosis or prophylaxis prior to admission were excluded. Each of the study arms included 155 patients.
The frequency of CDI treatment initiation was the study’s primary outcome. CDI positivity type, CDI antibiotic days, all-cause in-hospital mortality, length of stay in days, frequency of infectious diseases and gastroenterology consults, and antimicrobial stewardship program (ASP) interventions were secondary outcomes.
In the one-step compared with the two-step group, CDI treatment initiation was higher (n=154 [99%] vs. n=122 [79%]; P<0.0001, respectively). They observed detection of community-associated CDI and hospital-onset CDI (HO-CDI) was lower in the two-step group compared with the one-step arm.
“In terms of our primary outcomes, really what we were looking at is the frequency of CDI treatment initiation, which was about 100% of the time—actually 99%—in our one-step method, compared with 79% in our two-step method,” Dr. Knack said at ECCMID 2023.
“And we’re thinking this is likely due to more of a highlight on that toxin results, but also possibly because of antimicrobial stewardship intervention, which we did see go up compared from the one-step to the two-step group. So, more [ASP] intervention can potentially drive optimal diagnosis,” she said.
CDI antibiotic days were lower in the two-step arm for inpatients and outpatients (836 vs. 639 and 1,098 vs. 741, respectively).
The researchers reported the all-cause in-hospital mortality was similar between the one- and two-step groups (n=14 [9%] vs. n=9 [6%]; P=0.27, respectively), as well as median length of stay (five days for both) and frequency of ID consult (103 [66%] vs. 104 [67%]). With the two-step algorithm, the number of GI consults was lower (74 [48%] vs. 93 [60%]), and ASP intervention was higher (62 [40%] vs. 30 [19%]).
Compared with a one-step algorithm, a two-step strategy reduced unnecessary treatment, improved CDI detection and reduced the incidence of reportable HO-CDI, they said.
Comorbidities and rCDI
In a retrospective study, a different group of researchers sought to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; Rebyota, Ferring) for the treatment of rCDI (Open Forum Infect Dis 2023;10[5]:ofad171). Broad eligibility criteria allowed the researchers to mimic real-world practice.
The researchers identified adults ages 18 years and older with rCDI from five study sites who had been treated with RBL under the FDA’s discretion from Nov. 1, 2015, to Sept. 30, 2019.
All patients who were naive to previous RBL treatment and had comprehensive medical records for six months post-treatment were included in the primary safety set (Pss).
The primary treatment cohort consisted of 94 patients and the Pss had 64 patients with common comorbidities receiving diverse chronic therapies. These comorbid conditions included irritable bowel syndrome (21.9%), microscopic colitis (10.9%), Crohn’s disease (7.8%) and ulcerative colitis (6.3%). In addition, 17.2% of patients were prescribed medication capable of causing immunosuppression when they received RBL.
“People who experience recurrent C. diff infection often have chronic gastrointestinal conditions that can also cause uncomfortable and painful symptoms, making their infection-related symptoms even more difficult to manage,” said lead researcher Paul Feuerstadt, MD, FACG, AGAF, an assistant clinical professor of medicine at Yale School of Medicine, in New Haven, Conn. “This is the first analysis evaluating safety and efficacy of Rebyota in patients who are often seen in clinical practice struggling with other gastrointestinal illnesses in addition to C. diff infection, who may be able to prevent recurrence of C. diff infection with a microbiome-based treatment following antibiotics.”
In the Pss, 82.8% of patients who received RBL responded at eight weeks, nearly 90% of whom had a sustained response through six months. The researchers noted the number of RBL doses administered did not have a significant effect on outcomes.
Treatment-emergent adverse events (TEAEs) were mostly mild to moderate. They were also comparable among the comorbidity subgroups and overall population.
The most common TEAEs reported in the Pss were GI disorders, including abdominal pain (14.1%), diarrhea (14.1%), bloating (6.3%), gas (6.3%) and nausea (6.3%), and infections, including urinary tract infection (10.9%) and CDI.
“Of the people who develop C. diff, one in six will develop recurrence, and that’s usually within two months,” Thomas Moore, MD, FACP, FIDSA, a clinical professor of medicine at the University of Kansas School of Medicine-Wichita, told Infectious Disease Special Edition. “It’s hard to characterize in an objective way how detrimental it is because it’s really kind of a subjective question.”
The rediscovery of transfaunation and fecal transplants may be crucial for treating rCDI effectively. A large study from the Netherlands demonstrated the significant superiority of fecal transplant compared with oral vancomycin, according to Dr. Moore (N Engl J Med 2013;368[5]:407-415).
The ability to interrupt and halt repeated cycles of recurrent CDI has a huge impact on quality of life for people, he explained.
Dr. Feuerstadt reported financial relationships with Ferring, Merck, Seres and Takeda. Dr. Moore reported financial relationships with Rebiotix and Seres.
This article is from the August 2023 print issue.